The ability to learn and remember is a critical survival skill whether you are a human or a fly. This proposal will exploit the behavioral and genetic richness of Drosophila to define and understand neuronal circuits that link sleep and memory. Humans spend roughly one third of their lives asleep. Amazingly, there is no consensus on why we and other animals sleep, only agreement that without sleep our brains do not function optimally. One recurring finding, with convincing data from humans, mammalian model systems, and Drosophila is that sleep is required for effective memory formation. We will investigate the role of the circadian clock in both sleep (Specific Aim #1) and memory formation (Specific Aim #2) using cell specific manipulations that alter neuronal excitability. We will identify and characterize the activity of cells that are downstream of the clock that generate sleep (Specific Aim #3). PUBLIC HEALTH RELEVANCE Lack of sleep is an increasingly serious human health problem in western society. Studies of the linkage between sleep and memory in Drosophila will provide insight into how sleep affects learning in humans.